According to the data released in 2011, a total of 218,017 cancer cases were reported to have occurred in South Korea in 2011. The crude incidence rates were 439.2 for male and 431.0 for female per 100,000 people. The order of incidence of cancer was stomach, colorectal, lung, liver, and breast cancer. The top 5 cancers describe above have more than 50% incidence rate of all cancers. The most common cancers for male were stomach, colorectal, lung, and liver cancer in sequence, and for female were breast, colorectal, stomach, and lung cancer except thyroid cancer. If South Korean people live to the average life expectancy, the chance of getting cancer will be 36.9%. It is assumed that 2 out of 5 males (38.1%) and 1 out of 3 females (33.8%) are likely to develop cancer. The age-standardized rate (ASR) in South Korea adjusted by world standard population was 295.1 per 100,000 people, which is lower than the figure for the U.S. (318.0) or Australia (323.0) but higher than the OECD average (271.5). According to the data from National Statistical Office, the number of deaths caused by cancer was 75,334 people in South Korea in 2013, accounting for 28.3% of total deaths, and it is expected that the death rate from cancer will increase by 8.8% over the 2 to 3 years. Therefore, in order to treat cancer with a high incidence and death rate, various methods of treatment are being attempted around the world. So far, surgery and anticancer drug therapy or radiation therapy are the best choices to treat the early and advanced stage cancer aggressively.
For surgical treatment of cancer, the class and type of tumor should be identified through the diagnosis of tumor. In most cases, a biopsy is performed for diagnosis. Surgery is the radical treatment that all of lymph nodes surrounding the tumor and primary lesions are removed, using the radical exeresis. The radical exeresis is preferentially conducted with the goal of complete recovery. The death rate due to exeresis has decreased to 1 to 3%, and the 5-year survival rate of patients has increased by more than 50%. However, it is well known that patients who underwent surgery have a risk of relapse. Further, the surgery may have acute side effects such as bleeding, intestinal obstruction, vascular injury, ureteral injury, rectal rupture, pneumonia, and pulmonary embolism caused by complications, and, thus, a reoperation may be needed. Chemotherapy is the treatment of disease using drugs, i.e., anticancer drugs, applied to cancer cells spread in the entire body. However, most of the anticancer drugs are prepared to suppress rapid growth of cancer cells and thus will cause damage to cancer cells and possibly also to normal cells to a lesser degree. Meanwhile normal cells, such as blood cells, epithelial cells of gastrointestinal tract including the oral cavity, hair cells, and reproductive cells that are rapidly divided or proliferated, are greatly affected, and, result in side effects such as anemia, hair loss, and genetopathy. In severe cases, the anticancer drugs may lower the function of the marrow and may cause infection within 2 to 3 weeks of treatment, leading to death from sepsis. Radiotherapy refers to the treatment of inducing apoptosis of cancer tissues with high energy radiation. This treatment is one of the methods that allows a patient to keep a normal life, but may cause damage to the normal skin in a local area as a side effect of high energy radiation. In cases of metastatic cancer, the cancer stem cells may be resistant to radiation and relapse or metastasis may occur.
In order to overcome these disadvantages, studies for developing a treatment method of combining radiotherapy with chemotherapy or gene therapy are actively conducted. For example, Korean Patent Laid-open Publication No. 2002-0042606 discloses a radiosensitizer composition containing an N-acetylphytosphingosine derivative and a dimethylphytosphingosine derivative, Korean Patent Laid-open Publication No. 2003-0055878 discloses a radiosensitizer containing ceramides and derivatives thereof and dimethylsphingosine which is a sphingosine kinase inhibitor, and Korean Patent No. 620751 discloses a composition for radiosensitization, containing paeonol and a pharmaceutically acceptable salt thereof as active ingredients. However, in cases of combining radiotherapy with the above-described anticancer drugs to improve therapeutic effects of the radiotherapy, toxicity of the anticancer drugs, such as inflammation at the radiation therapy site, gastric disorder, nausea, vomiting, and diarrhea, may occur in addition to the side effects of the radiotherapy. Thus, the use of anticancer drugs is limited. Furthermore, it is known that due to the immunosuppressive environment, tumor cannot be completely exterminated and the risk of relapse is high.
Accordingly, the development of a novel treatment that is easily applicable to treat cancer and capable of effectively treating cancer with less influence on normal tissues is urgently needed. According to results from recent studies, it is known that a cancer cell has its own characteristics and can continuously grow while maintaining the characteristics. Firstly, a cancer cell has a characteristic of continuously maintaining a differentiation signal. For example, cell differentiation and survival by maintaining a β-catenin signaling is well known. A normal cell inhibits overproduction of the β-catenin signaling through protein ubiquitination, whereas a cancer cell avoids β-catenin ubiquitination and continuously maintains a growth signal. Secondly, a cancer cell has a system for producing an excessive amount of lactic acid through glycolysis using glucose to produce energy with high efficiency. Thirdly, a cancer cell has a characteristic of avoiding apoptosis. By activating poly ADP ribose polymerase (PARP), an apoptosis escaping molecule, a cancer cell avoids apoptosis with a resistance to various gene-targeted treatments and continuously maintains tumor formation. Fourthly, cancer is excellent in invasion or metastasis and also capable of creating its own environment by angiogenesis. If cancer grows continuously, necrosis occurs around tumor and the oxygen supply is reduced causing the increase of hypoxia inducible factor (HIF)-1α that is known to involve the above phenomenon directly or indirectly.
Targeting the above-described characteristics of cancer, various anticancer drugs have been developed based on regulation of cell growth and metastasis suppression. However, tyrosine kinase inhibitors mediating growth signals have shown unsatisfactory treatment results and resistance to drugs. In the development of anticancer drugs, it is still difficult to find a method to effectively suppress growth of cancer cells regulated by a network of complicated signaling pathways.
Under these circumstances, the inventors of the present disclosure studied and tried to develop a method to effectively suppress growth of cancer cells and treating cancer and as a result, completed the present disclosure by finding out that metal lactate salts capable of dissociating lactate, which can disturb metabolism of cancer cells and thus effectively inhibit activities such as growth, invasion, and metastasis of the cancer cells within the cancer cells, can be used as active ingredients of an anticancer drug.